Progress in FY2014 was in the following areas: LOW COMPLEXITY SEQUENCES. In collaboration with Prof. Steven McKnight (UT Southwestern Medical Center) and his colleagues, we have performed solid state NMR measurements on fibrils formed by low complexity (LC) sequences of hnRNPA2 and FUS, which are likely to be related to protein aggregates implicated in ALS, FTD. For both hnRNPA2 and FUS LC fibrils, 2D and 3D solid state NMR spectra indicate that only a fraction (20%) of the LC sequence forms the fibril core, with the remaining segments forming flexible loops outside the core. Solid state NMR measurements show that the core is an in-register, parallel cross-beta structure, as in many amyloid fibrils. Preliminary hydrogen-deuterium exchange data suggest that the core structure in LC fibrils may be significantly less stable than in disease-associated amyloid fibrils and prion fibrils, accounting for the transient nature of LC-LC association within normal cells. Efforts are underway to determine solid state NMR chemical shift assignments for FUS LC fibrils, and then develop a detailed molecular structural model. MAX1 HYDROGEL FIBRILS. In collaboration with Joel Schneider's group in NCI, we have developed a full structural model for fibrils formed by MAX1, a peptide designed by the Schneider group to form reversible hydrogels comprised of MAX1 fibril meshes. According to solid state NMR data, MAX1 adopts a well-defined beta-hairpin conformation in the fibrils, and beta-hairpins align in parallel with one another within beta-sheet layers. Each fibril contains at least two such layers, stacked in such a way that there is an overall 2-fold symmetry axis parallel the fibril growth axis. This experimentally-based model supports the predictions of the Schneider group. It is the first concrete evidence for beta-hairpin conformations within amyloid-like fibrils.